Implementing Project BioShield: Government Goals, Priorities and Programs

1. U.S. Department of Health and Human Services Office of Public Health Emergency Preparedness Implementing Project BioShield:Government Goals, Priorities and Programs Monique K. Mansoura, Ph.D. Office of Research and Development Coordination NVAC Meeting 6 October 2004 Enter Title of Presentation on Master Slide

2. Biodefense for the US Government Unprecedented opportunity • A top priority and dedicated commitment among senior leaders of this Administration • Generous bipartisan support from Congress • Solid scientific foundation • Due in large part to the research that has been developed over many years at USAMRIID • Rapidly increasing database of basic research information about pathogens using 21st century biotechnologies such as genomics • A strong private sector

3. Biodefense for the 21st Century • This Presidential Directive follows a comprehensive evaluation of biological defense capabilities and provides a blueprint for our future biodefense program. • On 28 April 2004, HHS Secretary Tommy G. Thompson along with DHS Secretary Tom Ridge and DoD Deputy Secretary Paul Wolfowitz, announced the presidential directive “Biodefense for the 21st Century.”

4. Biodefense for the 21st Century • Essential Pillars of national biodefense • Threat Awareness • Anticipation of Future Threats • Prevention and Detection • Surveillance and Detection • Response and Recovery • Capabilities required for response will be based on interagency-agreed scenarios that are derived from plausible threat assessments. • Mass Casualty Care • Risk Communication • Decontamination • MEDICAL COUNTERMEASURE DEVELOPMENT • HHS will continue to lead the effort to ensure the development and availability of sufficient quantities of safe and effective medical countermeasures to mitigate illness and death in the event of a biological weapons attack.

5. Government Goals: Medical Countermeasures • Develop, acquire, and stockpile the medical countermeasures needed to protect the U.S population against bioterrorism • Coordinate stockpile acquisitions with response plans • Make balanced investments in countermeasures commensurate with the threat(s) and responseplans and within the limits of the budget

6. Purpose: To accelerate the process of research, development, purchase, and availability of effective countermeasures against agents of bioterror. Project BioShield Announced by President Bush in his State of the Union address on 28 January 2003. • Secretaries Thompson (HHS) and Ridge (DHS) jointly transmitted the “Project BioShield Act of 2003 to Congress on 26 February 2003. • - The House version of the bill (H.R. 2122) was passed by a vote of 421-2 on 16 July 2003. • The Senate version of the bill (S. 15) was passed by a vote of 99-0 on 19 May 2004. • The bill (P.L. 108-276) was signed by the President on 21 July 2004

7. Project BioShield President George W. Bush signs S.15-Project BioShield Act of 2004, in the Rose Garden Wednesday, July 21, 2004

8. Project BioShield Three-pronged program: • Establishes a secure funding source for purchase of critical biomedical countermeasures • Increases NIH/NIAID authorities and flexibility to expedite research and development of critical biomedical countermeasures • Establishes a FDA Emergency Use Authorization for critical biomedical countermeasures

9. Emergency Use Authorization (EUA) • Minimizes regulatory burden during a declared emergency. • Serious/life-threatening condition caused by biologic, chemical, radiological/nuclear substance. • Reasonable to believe that product may be effective. • Known or potential benefits outweigh known or potential risks. • No adequate alternative that is approved and available. • Applicability for drugs, vaccines, devices: • Approved product for an unapproved indication. • Unapproved product

10. Project BioShield • The DHS appropriations bill (PL 108-90) signed by President Bush on 1 October 2003 created a discretionary reserve of $5.6 billion to fund the program through FY2013. An amount not to exceed $3.4 billion may be obligated during FY2004-2008. • Funding is available for countermeasures once production of licensable products is judged scientifically feasible. HHS will be the procuring authority. • Amounts appropriated become available only upon the approval by the President.

11. Medical Countermeasures Pipeline Procurement via BioShield

12. Build Research Infrastructure • Conduct Basic Research • Develop Medical Countermeasures NIH • Strategic National Stockpile (SNS) • Train Local Response Teams • Surveillance and Detection CDC BioShield Implementation: Coordination within HHS O P H E P • Regulatory Approval • Vaccines, Therapeutics, Diagnostics FDA • Acquire Medical Countermeasures • - Execute Project BioShield ORDC

13. BioShield:Interagency coordination POTUS Principals Deputies Counterproliferation Technology Coordinating Committee (NSPD-17/HSPD-4) HHS has a leadership role in the WMD Medical Countermeasures Subcommittee This interagency group will coordinate national requirements, acquisition strategies, and requests for Project BioShield funding CTWG Intel Non Medical CM Detector/ Surveillance Counter Force WMD Medical CM BIOLOGICAL CHEMICAL RAD / NUC Vaccines, Therapeutics, Diagnostics

14. Government Stakeholders Department of Health and Human Services Department of Homeland Security Department of Defense (Centers for Disease Control and Prevention) (Food and Drug Administration) (National Institutes of Health) Department of Agriculture Department of Commerce Department of Energy Department of Veterans Affairs Environmental Protection Agency National Space and Aeronautics Administration Intelligence Community (FBI, CIA) Homeland Security Council National Security Council Office of the Vice President Office of Science and Technology Policy Office of Management and Budget

15. WMD Medical Countermeasures Subcommittee Goals • Prioritize federal initiatives • Address immediate and long-term needs • Recommend national requirements for vaccines, drugs, antitoxins, diagnostics • Represent needs of civilian and military • Coordinate research, development, and acquisition efforts of key federal agencies: HHS, DHS, and DoD • Accelerate development of critical products

16. Factors Considered in Developing Requirements • Credibility and immediacy of threat • Target population • Who is targeted (civilian, military, high risk groups, other)? • In what settings would the countermeasure be used? • Availability of alternative countermeasures • Current and projected • Dosing schedule for prevention or treatment • Feasibility of deployment in a public health emergency • Product shelf-life and ongoing requirements

17. Evaluating the Effectiveness of Countermeasures • Modeling medical consequences and effectiveness of response • HHS responsibility • Uses mathematical models to estimate casualties from an attack scenario and impact on the medical care system • Can be used to evaluate the effectiveness of various medical countermeasures • Pre-event vaccination, Post-exposure vaccination, Post-exposure antibiotics, Quarantine and isolation • Value of the models is dependent on the validity of the assumptions • Highly sensitive to estimations of infectious dose, transmission rate, incubation period • Knowledge gaps become evident and inform research agenda • HHS has begun a program to develop the best models for evaluation of medical countermeasures

18. Release of BioShield Funds • Interagency Approval of Requirement • Findings by Secretaries of DHS and HHS • Determination of material threat • Countermeasures are necessary • Appropriateness of the countermeasure • Numbers of doses required • Production & delivery is feasible within 8 years • Evaluation of commercial market • Approval by the President

19. Contract Terms for Project BioShield • No payment may be made until delivery has been made of a portion of the total number of units contracts for • Discounted payment for product that is not licensed, cleared, or approved at the time of delivery. • Delivery to the SNS is contingent on the availability of sufficient data to support emergency use • Vendor must seek approval, clearance, or licensure of product. • Additional payment upon licensure, clearance or approval • Contract duration will be 5-8 years

20. Conditions for BioShield Acquisitions • Requirement that product will be approved or licensed within 8 years • A judgment based on the development status • Included in the Secretary’s determination • Requires sufficient data to assure there are no major obstacles to licensure • Toxicology • Phase 1 trial • Pharmacokinetics or immunogenicity • Animal studies of efficacy • Demonstration of manufacturing capability • Products in early development are ineligible • Early and mid stage development must be funded by other government programs or industry

21. Timeline for Anthrax rPA Vaccine Development Large-scale Manufacturing RFP ORDC 04-01 Published Anthrax Attacks NIAID 03-29 contracts awarded Fill/Finish 2000 doses NIAID 02-26 RFP for rPA 10/01 2/02 4/02 9/02 3/03 5/03 8/03 9/03 3/04 Large-scale Acquisition NIAID draft RFP for rPA NIAID 02-26 contracts awarded NIAID 03-29 RFP for rPA HHS RFI for large-scale manufacturing capacity

22. Project BioShield ProcurementsAcquisition of rPA Anthrax Vaccine for the Strategic National Stockpile • RFI issued in August 2003 to collect information about large-scale manufacturing capabilities for next generation anthrax vaccines • RFP Issued 3/11/04; Proposals Received 4/23/04 • Solicitation Number RFP-DHHS-ORDC-04-01 (http://www.fedbizopps.gov/) • Deliverables include: • Up to 75 million doses for rPA Anthrax vaccine, 25 million doses to be delivered within 2 years of contract award • FDA approval letter for the BLA for pre-exposure prophylaxis • FDA approval letter for the BLA supplement for post-exposure prophylaxis • Ongoing Quality Control/Quality Assurance monitoring of SNS stored product and ongoing stability testing of the retained lots of product in SNS • Submission of final study reports as evidence of completion for special population trials, including pediatric and geriatric populations • One (1) lot of Bulk Drug Substance per year to maintain cGMP capacity (warm base) for the production of rPA anthrax vaccine for the life of the contract

23. Project BioShield ProcurementsAcquisition of Therapeutic Products for Treatment of Inhalational Anthrax Disease • RFP issued 8/18/04; proposals due 10/26/04 • Solicitation Number 2004-N-01385 (http://www.fedbizopps.gov/) • Acquisition of therapeutic products for the SNS to treat inhalational anthrax disease: • Immune globulin and polyclonal antibodies • Monoclonal antibodies • Non-antibody toxin inhibitors, e.g. small molecular entities • Sample purchase for comparative testing by USG • Subsequent acquisition of 10,000-200,000 therapeutic courses of treatment from one or more producers